The expansion of access to ART has the potential to greatly benefit the physical, social and economic well being of individuals and households, as well as produce unintended negative consequences with regard to increased risk behavior and social disruption which can compromise its effectiveness. Drawing on Social Cognitive Theory, the proposed 4-year study will examine (1) how depression influences multiple health outcomes of patients and their households including economic output, household constellation, children's school attendance, and sexual risk behaviors, both directly and as a moderator of impact of ART;and (2) the impact of antidepressant treatment in mitigating the negative consequences of depression on these health outcomes in the context of ART scale-up in Uganda. The study will consist of two phases. In Phase 1, semi- structured qualitative interviews with ART patients, clinic providers, administrators, and support service organizations will be used to explore (1) the impact of HIV and ART on patients'physical, mental, social, economic and sexual health;(2) how mental health and depression influence these ART outcomes;and (3) attitudes towards and acceptability of depression treatment and antidepressants. Findings will help develop and refine hypotheses and measures for use in Phase 2. In Phase 2, patients entering HIV care and starting ART will be followed for 12 months in a longitudinal prospective cohort study. Those diagnosed with depression will be offered antidepressant treatment. Data from our two other just-funded observational cohort studies of ART and non-ART patients in Uganda, which include a subgroup of patients who are depressed but not receiving depression treatment, will provide important additional comparative data for evaluating the effects of depression and antidepressant therapy. These findings could provide critical information for the development of interventions and public health policy aimed at maximizing the benefits of ART in limiting HIV transmission and the social and economic consequences of the epidemic in the developing world, including the prioritization of improved diagnosis and treatment of depression. PUBLIC HEALTH RELEVANCE: This study is important to public health as its findings could provide critical information for the development of interventions and public health policy aimed at maximizing the benefits of ART in limiting HIV transmission and the social and economic consequences of the epidemic in the developing world, including the prioritization of improved diagnosis and treatment of depression.